Evaluation of HCC Screening Program with Abdominal Sonography for Subjects Identified from Their Family Index HCC Cases
Date Issued
2009
Date
2009
Author(s)
Wang, Lei-Ling
Abstract
Background In addition to other risk factors such as HBV and HCV infection, family history is also demonstrated to be associated with the risk of hepatocellular carcinoma (HCC). Therefore, screening for high-risk subjects ascertained through family index case with sonography is regarded as one of approaches to identify early-detected HCC cases. Evaluation of effectiveness of ultrasonography screening and the better understanding of disease progression of HCC using such kind of data have significant implication for early detection of HCC cases among these high-risk subjects.ims The aims of this study are therefore to 1)assess whether an index approach has a high yield of detecting HCC cases compared with the routine-finding in the absence of organized screening program;2)elucidate the association between demographic features, ALT, AST, alpha-fetoprotein, degrees of relative relationship, and occurrence of HCC cases or deaths; 3)quantify the disease natural history of HCC disease progression, the program sensitivity, and positive predictive value;4)project mortality reduction as a result of ultrasonography screening with adjustment for these putative risk factors and lead-time bias. ethods A total of 20,348 first- or second-degree relatives of patients with HCC diagnosed in multiple hospitals were enrolled in a multicentre hospital-based ultrasonography screening between 1992 and 1997. The cohort was linked with Taiwan Cancer Registry and Taiwan Mortality Registry for further confirmation of clinically-detected cases and death. We used logistic regression to identify factors affecting the detection in the prevalent screen, and proportional hazards regression models for the factors affecting the incidence of and mortality from HCC. Two statistical models, early indicator of the proportion of post-screening cases to the expected incidence rate conjugated with Poisson model and multi-state stochastic modeling, were used to estimate mean sojourn time (MST), sensitivity, and positive predictive values of the screening program. esults After adjusting for the well-established biological environmental factors, we found degrees of relative relationship was significantly associated with cases detected in the screening (odds ratio (OR)=4.0 (95% confidence interval : 1.84-8.53) for siblings compared to offspring, and 4.16 (95% confidence interval : 1.35-12.88) for parents compared to offspring). For the incidence of interval cancer or post-screening cases, degrees of relative relationship were also significant factors (hazard ratio (HR) of siblings versus offspring was 1.82 (95% confidence interval : 1.49-2.21), and of parents versus offspring was 1.62 (95% confidence interval : 1.14-2.31). However, it is not significantly associated with survival of HCC. Level of education was found associated with HCC survival. The lower level of education, the poorer survival was found. egarding the screening findings, the detection rate at prevalence screen was 2 per 1000 (41/20348). It decreased to 0.93 per 1000, and 0.75 per 1000 at the second and third or further subsequent screening. The incidence rate of interval cancer and post screening cases were 1.87 and 2.10, respectively. As regards the efficacy of screening with ultrasonography, compared to post-screening cases, screening detected and interval cancers combined had a 27% lower risk of dying from HCC (95% confidence interval : 1%-46%), with adjustment for other biological environmental risk factores, degrees of relative relationship and lead-time. he estimated mean sojourn time and sensitivity were 0.35 years and 61.2% with Poisson model, and 0.76 and 79.4% with the multistate stochastic model. The MST together with the program sensitivity yielded 24.2% and 67.7% of two positive predictive values for the Poisson model and three-state stochastic model, respectively. onclusion This study demonstrated ultrasonography screening can lead to a 27% (95% confidence interval : 1%-46%) statistically significant mortality reduction with adjustment for family history, other environmental factors, and lead time obtained from natural history. The estimated parameters of disease natural history suggests the intensive screening may even lead to a large benefit.
Subjects
HCC
Abdominal Sonography
Evaluation of Screening Program
SDGs
Type
thesis
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